Receptor tyrosine kinases (RTKs) are vital mediators of extracellular signals, which direct cell growth, survival and motility pathways. Several pathogenesis including chromosomal rearrangements, gene amplification, and point mutations result in abnormal and constitutive RTK activation which is in turn responsible for initiation and progression of many cancers, including non-small cell lung cancer (NSCLC). The first targetable fusion gene of RTK identified in NSCLC is Echinoderm microtubule associated protein like 4 ((EML4)-ALK). Oncogenic c-ros oncogene1 (ROS1) RTK is later reported to be fused with other forms of lung constitutive expressed 5′ or 3′-fusion gene partners in NSCLC. Approximately 1˜2% of NSCLC patients harbor multiple kinds of ROS1 chromosome rearrangement. Recent developments in targeted-based therapies have led to a major paradigm shift in oncology. Small-molecule tyrosine kinase inhibitors are applied to treat cancer patients who have tyrosine kinase gene fusions. Several tyrosine kinase inhibitors have been shown to have promising effect in the clinical practice. For example, Crizotinib, a potent ATP-competitive small molecule inhibitor of ALK, have now been approved by the FDA for treating NSCLC patients that are ALK rearrangement-positive. Crizotinib displays marked anti-tumor activity both in vitro and in vivo as well as in clinical practices. Since the tyrosine kinase domains of ALK and ROS1 are very similar, with 77% identity within the ATP-binding sites, most ALK inhibitors have cross activity against ROS1. In one early clinical trial of crizotinib to treat NSCLC patients harboring ROS1 rearrangements, the objective response rate was 72%, the median duration of response was 17.6 months and median progression-free survival was 19.2 months. Although most patients with ROS1-positive NSCLC exhibit substantial clinical benefit from Crizotinib, the efficacy of Crizotinib is limited by the development of acquired drug resistance. Accordingly, there is a need for new compound targeting ROS1 for cancer treatment.